tbuckley/cabot-search huggingface dataset:
AB0190 GENDER DIFFERENCES IN OSTEOPOROSIS RISK FACTORS IN PATIENTS WITH RHEUMATOID ARTHRITIS REFERRED FOR BONE DENSITY ESTIMATION – AN OBSERVATIONAL STUDY
Authors: M. D. Bokobza de la Rosa, Z. Sultan, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with a loss of bone density and fragility fractures [1]. There are few studies that compare bone loss by gender. <h3>Objectives</h3> This study aims to explore the bone loss by gender in a large RA cohort referred for bone mineral density (BMD) estimation. <h3>Methods</h3> RA patients referred to a district BMD scanner in the northwest of England between 2004 and 2019 were included. The cohort was divided by gender and the prevalence of fracture, and risk factors for fractures modelled. Initially, traditional risk factors as defined by FRAX(tm) were compared between men and women and subsequently the ability of those risks to predict fractures were modelled. For the characteristic of secondary osteoporosis, only coeliac disease was included. Comparison was made using Chi-squared test for categorical variables and T-test for continuous variables. Predictors of fracture were modelled using logistic regression. <h3>Results</h3> 2072 patients, mean age 66.97 years (s.d. 11.34) were included, of whom 1628 (78.6%) were females. The mean age was significantly higher in Males at 68.02yrs compared to Females at 66.69yrs (p=0.0284). Height (171.62cm) and Weight (80.97) was higher in males and History of fractures was higher in females (33.11% vs 23.42% - p&lt;0.001). Excess alcohol (6.08% vs 2.58% - p&lt;0.001) and Steroid therapy (46.4% vs 28.62% - p&lt;0.001) were higher in men. All other characteristics had no significant difference except lumbar spine BMD which was higher in men (-0.24 vs -0.82 - p&lt;0.001). A summary of the differences is shown in Table 1. <h3>Conclusion</h3> The study identifies gender differences in the risk factors for fractures in rheumatoid arthritis patients. This will have implications when assessing fracture risk using FRAX(tm) underestimating fracture risk in this population. FHx of fractures was only significant in fractured RA females. Steroid therapy had an idiosyncratic effect and was seen as protective; this was previously described in this cohort [3]. Being a current smoker was only a significant risk factor in males. Finally, Left and Right NOF and lumbar spine BMD were significantly smaller in both fractured genders making a reduced BMD on these sites an important risk factor to consider in any patient with RA. The strength of this study was the large cohort of rheumatoid arthritis patients included while it was limited by lack of detail on disease activity, treatment and duration. A variety of significant data was found, but further work is required to find accurate differences between the risk factors associated with fractures in both genders with RA. <h3>References</h3> [1]Wysham KD et al, Current Opinion in Rheumatology. 2021;33(3):270–6. [2]Bukhari M et al, Rheumatology Advances in Practice. 2021Nov16;6(2). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0057 ESTABLISHMENT OF NOVEL 3D SPHEROID-BASED MODEL OF RHEUMATOID ARTHRITIS SYNOVIAL TISSUE TO INVESTIGATE THE INTERACTION BETWEEN DIFFERENT CELL TYPES
Authors: E. Philippon, J. P. Van Hamburg, F. Khodadustvaskasi, L. Van Rooijen, C. J. Van der Laken, S. Tas
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid Arthritis (RA) is a progressive and systemic autoimmune disorder associated with chronic and destructive inflammation of the joints. The hallmarks of RA are synovial cell proliferation, extensive neoangiogenesis and infiltration of numerous immune cells into the synovial tissue. <i>In vitro</i> approaches simulating RA synovial tissue are crucial in preclinical and translational research to expand our knowledge on RA human pathophysiology and to test new diagnostic and therapeutic applications. <h3>Objectives</h3> Here, we present the engineering of a spheroid-based model of RA synovial tissue which mimics the close interaction between cells and key pro-inflammatory mediators present in the inflamed synovium. <h3>Methods</h3> Following differentiation in 20 ng/ml GM-CSF for 6-7 days, monocyte-derived macrophages were cultured with RA fibroblast-like-synoviocytes (RA-FLSs) and endothelial cells (ECs) for 24 hours to allow for spheroid formation. Three RA-FLS/EC/macrophage ratios were tested: (1:2:0.4), (1:2:0.8) and (1:2:1.6). Then, the spheroids were placed in a collagen-based matrix for 40 hours to study spheroid outgrowth in 3 dimensions. The spheroids were left unstimulated, or cultured in the presence of growth factors VEGF/bFGF or RA synovial fluid. Sprout formation and cell migration were quantified for all conditions using confocal microscopy and digital image analysis. <h3>Results</h3> Addition of macrophages to the previously established 3D model of RA angiogenesis consisting of ECs and RA-FLSs resulted in close interaction of macrophages with RA-FLSs and ECs within the spheroid structure. The optimal ratio between RA-FLSs, ECs and macrophages in our system was established as 1:2:0.8, based on the proportions of macrophages that remained within the core and migrated throughout the matrix as well as the effect of stimuli on sprout formation. Addition of growth factors (VEGF/bFGF) significantly promoted spheroid outgrowth compared to the unstimulated condition in the new model <i>(p&lt;0.01</i>). <h3>Conclusion</h3> We present a novel 3D-spheroid based model consisting of RA-FLSs, ECs and macrophages that mimics the RA synovial tissue microenvironment. This model is useful to dissect the role of specific cell types in inflammatory responses in RA, to study specific signaling pathways involved in the disease pathogenesis and examine the potential of novel diagnostic (molecular imaging) and therapeutic compounds, including small molecule inhibitors and biologics. <h3>Reference</h3> [1]Maracle, C.X., et al., <i>Targeting non-canonical nuclear factor-kappaB signalling attenuates neovascularization in a novel 3D model of rheumatoid arthritis synovial angiogenesis.</i> Rheumatology (Oxford), 2017. <b>56</b>(2): p. 294-302. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0099 CLONORCHIS SINENSIS-EXCRETORY/SECRETORY PROTEIN AMELIORATES INFLAMMATION IN ANKYLOSING SPONDYLITIS
Authors: Y. J. Lee, M. J. Kim, H. I. Lee, S. C. Shim, E. J. Won, T. J. Kim
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ankylosing spondylitis (AS) is a sort of inflammatory arthritis that affects axial skeleton, peripheral joints, and certain extra-articular organs, including the eyes, skin, and gut. Recently, many attempts have been made to use parasite administration (e.g., ingestion of eggs of the nematode Trichuris suis) as a new modality for treating inflammatory disorders. Our group published that Clonorchis sinensis protein attenuated inflammation in AS. <h3>Objectives</h3> Thus, this study aimed to assess the therapeutic potential of Clonorchis sinensis-Excretory/Secretory protein (Cs-ESP) for AS. <h3>Methods</h3> Cytotoxicity of Cs-ESP at different doses was assessed by MTS and flow cytometry before performing experiments. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analyzed using flow cytometry. The levels of INF-g, IL-17A, TNF-a, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). SKG mice were treated with Cs-ESP or vehicles. Inflammation was evaluated using immunohistochemistry. <h3>Results</h3> Treatment with Cs-ESP resulted in no reduced cell viability of PBMCs or SFMCs. In experiments culturing PBMCs and SFMCs, the frequencies of IFN-g and IL-17A producing cells were significantly reduced after Cs-ESP treatment. In the SKG mouse model, Cs-ESP treatment significantly suppressed arthritis and enthesitis. <h3>Conclusion</h3> We provide the evidence demonstrating that Cs-ESP can ameliorate clinical signs and cytokine derangements in AS. <h3>References</h3> [1]Kim TJ, Kim TH. Clinical spectrum of ankylosing spondylitis in Korea. Joint Bone Spine (2010) 77(3):235–40. [2]Martinez FD. The coming-of-age of the hygiene hypothesis. Respir Res (2001) 2(3):129–32. [3]Summers RW, Elliott DE, Urban JF Jr., Thompson RA, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology (2005) 128(4):825–32. [4]Osada Y, Shimizu S, Kumagai T, Yamada S, Kanazawa T. Schistosoma mansoni infection reduces severity of collagen-induced arthritis via downregulation of pro-inflammatory mediators. Int J Parasitol (2009) 39(4):457– 64. [5]Song X, Shen J, Wen H, Zhong Z, Luo Q, Chu D, et al. Impact of Schistosoma japonicum infection on collagen-induced arthritis in DBA/1 mice: a murine model of human rheumatoid arthritis. PloS One (2011) 6(8):e23453. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0119 EVALUATION OF P-GP AND MRP-1 EXPRESSION ON PLASMA CELLS AND TH17 LYMPHOCYTES IN PERIPHERAL BLOOD AND BONE MARROW OF LUPUS NEPHRITIS
Authors: K. Singh, D. P. Misra, S. Katiyar, V. Agarwal
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> P-glycoprotein (p-gp) and multidrug resistance protein 1 (MRP-1) contribute towards resistance to glucocorticoids and/or immunosuppressive drugs in lupus nephritis (LN). Long-lived plasma cells (PCs) persistently produce antibodies and are resistant to most immunosuppressive therapies including B-cell depletion. Elevated T helper 17 lymphocytes (Th17) are associated with resistant LN phenotypes. We hypothesize the overexpression of p-gp and MRP-1 on these two cell types which might eventually contribute towards drug-resistant phenotype in LN. <h3>Objectives:</h3> 1.To evaluate the frequency of peripheral blood PCs and Th17 cells expressing p-gp and MRP-1 in LN compared with healthy controls (HCs). 2.To evaluate the frequency of PCs expressing p-gp in bone marrow of LN. <h3>Methods</h3> Patients with LN fulfilling the 2019 ACR/EULAR classification criteria and HCs were recruited after written informed consent. p-gp and MRP-1 expression on peripheral PCs (CD45+ CD138+), p-gp expression on Th17 (CD4+ IL-17+ p-gp), Th1 (CD4+IFN-γ), Th2 (CD4+ IL-4) and regulatory T lymphocytes (Tregs, CD4+ CD25+ FoxP3+) were determined using flowcytometry (BD FACS Canto II). Proportions of T lymphocytes were normalized to Tregs. Frequencies of P-gp+ PCs were enumerated in bone marrow aspirate of two patients and one control. Results were expressed as median (interquartile range, IQR). Inter-group comparisons were performed with Mann-Whitney U test. p-value were corrected for multiple testing using Bonferroni-Sidak method. Statistical significance was set at p&lt;0.05. <h3>Results</h3> Twenty-one LN [17 females, median (interquartile range – IQR) age 26 (23.25-35) years] and 10 controls [7 females, median (IQR) age 28 (27–31) years] were recruited. Of 21 LN, 13 had active disease (66% had low complements, 59% had elevated anti-dsDNA). Median SLEDAI-2K score of LN patients was 12 (2-21). In peripheral blood, overall PCs as well as PCs expressing P-gp or MRP-1 were increased in LN than in HC. Th17/Tregs ratio, p-gp-expressing Th17 lymphocytes and MRP-1-expressing Th17 lymphocytes were significantly increased in LN compared to HC (Table 1). p-gp expressing Th17 lymphocytes and PCs were significantly increased in active LN than in inactive LN (Table 1). As an exploratory analysis, p-gp-expressing PCs were more prevalent in bone marrow aspirate of LN than non-lupus controls (Figure 1). <h3>Conclusion</h3> We observed for the first time an increased frequency of P-gp and MRP-1-expressing PCs and Th17 lymphocytes in the peripheral blood of LN, which were also associated with disease activity. Whether these cell populations contribute to refractory LN requires evaluation. <h3>Acknowledgements</h3> Funding from Indian Council of Medical Research (ICMR) – grant number No. 3/1/1(20)/2022-NCD-I. <h3>Disclosure of Interests</h3> None Declared.
AB0107 A CAUSAL EFFECT OF IL-10 LEVELS ON THE RISK OF ANKYLOSING SPONDYLITIS: A MENDELIAN RANDOMIZATION STUDY
Authors: Y. X. Chen, J. Q. Bai, C. Wang, L. L. Zheng, J. Qiao, S. X. Zhang, Q. Yu, P. F. He
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ankylosing spondylitis (AS) is a chronic inflammatory immune response disease mainly presenting with fibrosis of the sacroiliac joint and calcification <sup>[1]</sup>. Interleukin-10 (IL-10) is a factor that suppresses Th17 cell activity and induced Treg cells to achieve immunosuppression. Observational studies show that IL-10 may be one of the important contributing sources of important inflammatory cytokines for AS <sup>[2]</sup>, but the causal relationship between them is not clear. <h3>Objectives</h3> The objective was to investigate the casual association between AS and IL-10. <h3>Methods</h3> The GWAS summary statistics of IL-10 and AS (Ncase = 968, Ncontrol = 336,191) were downloaded from the IEU GWAS database in the study. After a series of screens, SNPs strongly associated with exposure were included as instrumental variables(IVs). The results are from using robust analyses with three two-sample different assumptions (Inverse variance weighting (IVW), Weighted median (WM) and MR-Egger). Meanwhile, we used MR-Egger intercept test, Cochran'sQ test and leave-one-out sensitivity analysis for assessment to avoid the biasing effects of potential genetic variation, horizontal pleiotropy and heterogeneity. MR-PRESSO outlier test was used to identify and eliminate horizontal pleiotropy. <h3>Results</h3> Our result showed that the level of IL-10 has a causal relationship with the risk of developing AS (IVW: OR=0.9992, 95% confidence interval (CI) 0.9985-0.9999, P = 0.03, Figure 1a, 1b). Increasing the IL-10 level can reduce the risk of AS disease. MR-Egger intercept test (MR-Egger intercept = -1.5705×10<sup>-5</sup>, P = 0.5158, Figure 1b), Cochran's Q test (IVW Q = 4.3071, Q_pval = 0.8284), leave-one-out sensitivity analysis (Figure 1c) and the funnel plot (Figure 1d) suggest almost no bias in the study, indicating that the MR was robust. <h3>Conclusion</h3> Our results indicate a protective role for IL-10 in AS, suggesting that elevated IL-10 levels may be able to alleviate the inflammatory response in AS, providing new insights into AS treatment. <h3>References</h3> [1]Braga, M.; Lara-Armi, F. F.; Neves, J. S. F., et al., Influence of IL10 (rs1800896) Polymorphism and TNF-α, IL-10, IL-17A, and IL-17F Serum Levels in Ankylosing Spondylitis. <i>Front Immunol</i><b>2021,</b><i>12</i>, 653611.doi:10.3389/fimmu.2021.653611 [2]Wu, X., Innate Lymphocytes in Inflammatory Arthritis. <i>Front Immunol</i><b>2020,</b><i>11</i>, 565275.doi:10.3389/fimmu.2020.565275 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0108 THE ASSOCIATION BETWEEN ELEVATED SERUM IL22 AND THE CLINICAL DIAGNOSIS OF AXIAL SPA.
Authors: K. Carpio, J. Pinto-Tasende, M. Fernandez-Moreno, M. E. Vazquez Mosquera, C. Fernández-López, N. Oreiro, F. J. De-Toro-Santos, F. J. Blanco
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Interleukin-22 (IL-22) is produced by T helper type 1, type 17, type 22 cells, and type 3 ILC, being probably a marker of osteogenic differentiation and new bone formation. Diagnosis and treatment are commonly delayed due to different clinical presentations that lead the patient to progressive articular damage. In recent studies, it seems that the serum levels of IL-22 are elevated in axial spondyloarthritis (AxSpA) and do not allow differentiation between AxSpA and other joint inflammatory disorders. <h3>Objectives</h3> The present research aimed to analyze serum cytokines as possible biomarkers regarding inflammation and bone destruction/regeneration in four rheumatic diseases. <h3>Methods</h3> Serum samples were acquired from patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and AxSpA. Serum levels of TGF-β1, IL-23, IL-6, IL-17A, IL-22, Dkk1, Sclerostin, BMP2, BMP4, Wnt1, and Wnt5a were measured by enzyme-linked immunosorbent assay (ELISA). All these data were analyzed and compared with the demographic, clinical, analytical, and radiological characteristics of the patients. Statistical analysis was performed using the SPSS version 23 program (IBM SPSS Statistics). Values of p &lt;0.05 were considered statistically significant. <h3>Results</h3> The serum samples were obtained from 35 patients (PsA n=11, RA n=7, OA n=13, AxSpA=4). All these patients were previously treated with NSAIDs and corticosteroids (oral/intraarticular); 4 were treated with csDMARDs, but no none of them was previously treated with biologics. IL-22 levels were higher in AxSpA patients (p= 0.046), although serum IL-22 levels did not correlate with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) (p = 0.154) or C-reactive protein (p = 0.208). The sensitivity and specificity of the serum IL-22 for the AxSpA diagnosis were 75% and 81% respectively, for the cut-off value of 58 ng/mL, with AUC 0.798 (95% CI 0.634-0.962 <h3>Conclusion</h3> Serum levels of IL-22 are elevated in patients with clinical diagnoses of AxSpA and could be an independent serum biomarker of this disease. <h3>Reference</h3> [1]Sagiv et al. Int J Rheum Dis 2022; 25: 56-60 <h3>Funding sources</h3> Grant (PI11/00390) from Plan Nacional de Investigación Científica, Desarrollo eInnovación Tecnológica 2008-2011 and co-financed by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación - Fondo Europeo de Desarrollo Regional (FEDER). <h3>Disclosure of Interests</h3> None Declared.
AB0139 VALIDATION AND THE CLINICAL UTILITY OF POLYGENIC RISK SCORING IN ASIAN SLE
Authors: W. T. Hung, Y. M. Chen, K. T. Tang, Y. J. Chen, Y. D. Wu, Y. W. Liao
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease with a complex pathogenesis. The etiology of SLE is multifactorial, and includes contributions from genetic, epigenetic, environmental, hormonal, and immune regulatory factors. The hereditary pattern of the disease is polygenic in most patients. A polygenic risk scoring (PRS) model has been used to estimate the genetic risk of SLE in individuals. This approach assumes independent and additive contribution of genetic variants to disease development. The Taiwan Precision Medicine Project (TPMI) in our hospital invited patients with various diseases to participate in the research project. We had collected and analyzed clinical data from electric medical records. We had also established SLE-PRS risk analysis for our TPMI cohort. <h3>Objectives</h3> To validate the clinical utility of PRS in Asian SLE. <h3>Methods</h3> To understand the clinical characteristics of individuals with high SLE-PRS, we recruited female individuals, aged 20-50, from the top 5% subjects with the highest SLE-PRS from TPMI cohort. Pre-existing diagnosis of SLE was excluded (Figure 1). Questionnaire was assessed with self-reported symptom. Autoantibodies and serum complement levels were also assessed. <h3>Results</h3> Among 442 patients had high SLE-PRS, we included 131 patients in our study. Antinuclear antibody detection rate was 37.3%. 16.8% of recruited individuals had either low serum complements level or defected complement function (Table 1). Overall, 20.37% of individuals with high SLE-PRS had two immunological abnormalities by SLICC criteria, while 5.56% of individuals had more than three immunological abnormalities. <h3>Conclusion</h3> High SLE-PRS may be helpful for early lupus detection. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS1580 A CASE SERIES OF VEXAS SYNDROME IDENTIFIED IN THE WEST MIDLANDS, UNITED KINGDOM
Authors: M. Ford, T. Khan
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome was first described in 2020 when a mutation in ubiquitin activating enzyme 1 (UBA1) was identified in three patients [1]. This adult-onset autoinflammatory and haematological disease primarily affects males over the age of 50 years. The clinical features are diverse but commonly include skin lesions, non-infectious fever, weight loss, lung involvement, arthralgia/arthritis, relapsing chondritis, ocular symptoms, venous thrombosis, and lymphadenopathy [2]. Whilst corticosteroids are effective, high doses are often required to control the disease and the ideal standard of care, including the choice and efficacy of steroid-sparing agents, is yet to be defined. <h3>Objectives</h3> After identifying three cases of VEXAS in our region within a 6-month period, our objective was to present each case alongside the current knowledge of the condition in order to increase the awareness amongst clinicians. <h3>Methods</h3> We examined each case, comparing the clinical features, investigations, management, and events leading to the diagnosis. <h3>Results</h3> The cases are presented in the table below. <h3>Conclusion</h3> The true prevalence of VEXAS is unknown however after we diagnosed three cases of the condition in a short period of time, it is perhaps more prevalent than initially thought. Clinicians should remain vigilant and consider genetic testing in patients presenting with the common inflammatory and haematological manifestations. <h3>References</h3> [1]Beck, D.B., Ferrada, M.A., Sikora, K.A., Ombrello, A.K., Collins, J.C., Pei, W., Balanda, N., Ross, D.L., Ospina Cardona, D., Wu, Z. and Patel, B., 2020. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. New England Journal of Medicine, 383(27), pp.2628-2638. [2]Al-Hakim, A. and Savic, S., 2022. An update on VEXAS syndrome, Expert Review of Clinical Immunology, DOI: 10.1080/1744666X.2023.2157262 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.